NCT03642626进行中（未招募）2 期
Chimeric Antigen Receptor (CAR)-T Cell Therapy for Patients With Hematologic Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Arms B & C&D& E&F: Overall Response Rate (ORR)
研究概览
简要总结
This is a phase II study of FDA-approved CAR-T products for patients with hematologic malignancies. Patients will be assigned to Arm A and B based on age and diagnosis. Overall remission rate, safety events and other endpoints will be calculated for Arm A and B separately.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ARM A (Kymriah) and Arm G (Tecartus) :Refractory/relapsed B-cell acute lymphoblastic leukemia expressing CD19
- •Inclusion Criteria:
- •Age and Disease Status
- •Must be age 0-25 years (for Arm A Kymriah) or >18 years (Arm G Tecartus)
- •Disease status: Relapsed and refractory pediatric B-cell ALL defined by one of these:
- •Primary induction failure with no complete remission after ≥2 cycles of induction chemotherapy, or
- •Patients with persistent minimal residual disease (MRD >0.01% by flow cytometry or persistent by cytogenetic or molecular assays) after ≥2 cycles of consolidation chemotherapy, or
- •Patients in 2nd or greater relapse of B-ALL or
- •Patients with persistent CNS leukemia, or
- •Down Syndrome or other congenital diseases assuming that they fit the criteria for second or greater relapse or refractory leukemia, or
- •Patients with Ph+ ALL are eligible if theywho have failed or are intolerant to two lines of TKI assuming they fit the criteria for second or greater relapse or are considered refractory.
- •Performance Status
- •* Arm A: Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50% at screening; Arm G: ECOG 0, 1 or 2
- •Organ Function
- •Renal function defined as:
- •A serum creatinine of ≤1.5 x ULN OR
- •eGFR ≥ 50 mL/min/1.73 m2
- •Liver function defined as:
- •** ALT ≤ 5 times the ULN for age (unless due to disease)
- •** Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
- •Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
- •Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
- •Other Inclusion Criteria
- •Life expectancy ≥12 weeks
- •Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
- •Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
排除标准
- •Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
- •Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
- •CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
- •Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
- •Uncontrolled active hepatitis B or hepatitis C
- •Active HIV infection
- •Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
- •Unstable angina and/or myocardial infarction within 1 month prior to CAR-T infusion
- •Investigational medicinal product within the last 7 days prior to apheresis or CAR-T infusion
- •Intolerance to the excipients of the CAR-T cell product
- •Any immunosuppressive medication must be stopped ≥ 2 weeks prior to enrollment.
- •Patient has taken one of the prohibited concomitant medications within the timeframe outlined in section 6.1
- •ARM B: Yescarta for Relapsed or Refractory diffuse large B cell lymphoma
- •Inclusion Criteria:
- •Age and Disease Status
- •Adult patients (age ≥ 18 years)Patients must be ≥18 years of age
- •One of the following histologies and expression of CD19 by tumor cells:
- •** diffuse large B-cell lymphoma (DLBCL) not otherwise specified, or
- •** primary mediastinal large B-cell lymphoma, or
- •** high grade B-cell lymphoma, or
- •** DLBCL arising from follicular lymphoma
- •Disease status:
- •** Chemotherapy refractory disease after ≥2 lines of chemotherapy, or
- •** Relapsed with no remission after ≥1 lines of salvage chemotherapy, or
- •** Relapsed following autologous HCT (and failed at least 2 prior lines of therapy including high dose chemotherapy). If salvage therapy is given post autoHCT, the subject must have no response or relapse after the last line of therapy
- •Measurable disease at time of apheresis: Nodal lesions or extranodal lesion
- •ECOG performance status 0-2
- •ALC >/=100/uL at screening (prior to apheresis)
- •Renal function defined as:
- •** A serum creatinine of ≤1.5 x ULN OR
- •** eGFR ≥ 50 mL/min/1.73 m2
- •Liver function defined as:
- •ALT ≤ 5 times the ULN for age (unless due to disease)
- •Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert syndrome; may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
- •Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation SpO2 > 91% on room air
- •Hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram or MUGA
- •Adequate bone marrow reserve (unless marrow infiltrated by disease) defined as :
- •Absolute neutrophil count (ANC) > 1.000/mm3 (only for NHL)
- •Platelets ≥ 50.000/mm3 (transfusion support can be provided)
- •Hemoglobin >8.0 mg/dl (transfusion support can be provided)
- •Life expectancy ≥12 weeks
- •Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.
- •Written voluntary consent (adults) or parental/guardian consent (minors or adults with diminished capacity) prior to the performance of any research related tests or procedures.
- •Exclusion Criteria:
- •Pregnant or breastfeeding - Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
- •Active CNS involvement by malignancy (no evidence of disease in CSF by flow cytometry) CAR-T is not indicated for the treatment of patients with primary central nervous system lymphoma.
- •Presence of Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD). All GVHD medication must be stopped 2 weeks prior to apheresis.
- •Uncontrolled active hepatitis B or hepatitis C
- •Active HIV infection (controlled HIV is permissible)
- •Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
- 另有 165 项未显示
研究组 & 干预措施
Arm F: Abecma for relapsed or refractory multiple myeloma
Experimental
干预措施: Cyclophosphamide 500 mg/m2; 3 doses (Drug)
Arm F: Abecma for relapsed or refractory multiple myeloma
Experimental
干预措施: Abecma, Intravenous Suspension (Drug)
Arm G: Tecartus B-cell acute lymphoblastic leukemia (ALL)
Experimental
干预措施: Fludarabine 25mg/m2 3 days (Drug)
ARM A: Refractory/relapsed B-cell acute lymphoblastic leukemia (ALL)
Experimental
干预措施: KYMRIAH (Drug)
ARM A: Refractory/relapsed B-cell acute lymphoblastic leukemia (ALL)
Experimental
干预措施: Fludarabine 30mg/m2 4 doses (Drug)
ARM A: Refractory/relapsed B-cell acute lymphoblastic leukemia (ALL)
Experimental
干预措施: Cyclophosphamide 500 mg/m2; 2 doses (Drug)
ARM B: Yescarta for Refractory diffuse large B cell lymphoma (DLBCL)
Experimental
干预措施: YESCARTA (Drug)
ARM B: Yescarta for Refractory diffuse large B cell lymphoma (DLBCL)
Experimental
干预措施: Fludarabine 30mg/m2 3 doses (Drug)
ARM B: Yescarta for Refractory diffuse large B cell lymphoma (DLBCL)
Experimental
干预措施: Cyclophosphamide 500 mg/m2; 3 doses (Drug)
ARM C: Kymriah for Refractory diffuse large B cell lymphoma (DLBCL)
Experimental
干预措施: KYMRIAH (Drug)
ARM C: Kymriah for Refractory diffuse large B cell lymphoma (DLBCL)
Experimental
干预措施: Fludarabine 25mg/m2 3 days (Drug)
ARM C: Kymriah for Refractory diffuse large B cell lymphoma (DLBCL)
Experimental
干预措施: Cyclophosphamide 250 mg/m2; 3 days (Drug)
Arm D: Tecartus CAR-T product for Mantle Cell Leukemia (MCL)
Experimental
干预措施: Fludarabine 30mg/m2 3 doses (Drug)
Arm D: Tecartus CAR-T product for Mantle Cell Leukemia (MCL)
Experimental
干预措施: Cyclophosphamide 500 mg/m2; 3 doses (Drug)
Arm D: Tecartus CAR-T product for Mantle Cell Leukemia (MCL)
Experimental
干预措施: Tecartus (Drug)
Arm E: Breyanzi for relapsed or refractory large B-cell lymphoma (RLBCL)
Experimental
干预措施: Fludarabine 30mg/m2 3 doses (Drug)
Arm E: Breyanzi for relapsed or refractory large B-cell lymphoma (RLBCL)
Experimental
干预措施: Cyclophosphamide 500 mg/m2; 3 doses (Drug)
Arm E: Breyanzi for relapsed or refractory large B-cell lymphoma (RLBCL)
Experimental
干预措施: Breyanzi Injectable Product (Drug)
Arm F: Abecma for relapsed or refractory multiple myeloma
Experimental
干预措施: Fludarabine 30mg/m2 3 doses (Drug)
Arm G: Tecartus B-cell acute lymphoblastic leukemia (ALL)
Experimental
干预措施: Tecartus (Drug)
Arm G: Tecartus B-cell acute lymphoblastic leukemia (ALL)
Experimental
干预措施: Cyclophosphamide 900 mg/m2; 1 day (Drug)
结局指标
主要结局
Arms B & C&D& E&F: Overall Response Rate (ORR)
时间窗: Day 100
ORR defined by complete response + partial response by Lugano
Arm A & E: MRD-negative CR (or CRi)
时间窗: Day 28
Percentage of patients with MRD-negative Complete Response CR (or CRi)
次要结局
- Treatment Related Mortality (TRM)(1 Year)
- Event-Free Survival (EFS)(1 Year post treatment)
- Percentage of Patients Developing Grade 3 or 4 ICANS(Day 28)
- Treatment Related Mortality (TRM)(Day 28)
- Treatment Related Mortality (TRM)(Day 100)
- Relapse-free Survival (RFS)(1 year)
- Overall Survival (OS)(1 year)
- Overall Toxicity(Day 28)
研究者
研究点 (1)
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